Abstract
Cadmium is a toxic metal and the mechanism of its toxicity has been studied in various model systems from bacteria to mammals. We employed Saccharomyces cerevisiae as a model system to study cadmium toxicity at the molecular level because it has been used to identify the molecular mechanisms of toxicity found in higher organisms. cDNA microarray and Northern blot analyses revealed that cadmium salts inhibited the expression of genes related to copper metabolism. Western blotting, Northern blotting and chromatin immunoprecipitation experiments indicated that CTR1 expression was inhibited at the transcriptional level through direct inhibition of the Mac1 transcriptional activator. The decreased expression of CTR1 results in cellular copper deficiency and inhibition of Fet3 activity, which eventually impairs iron uptake. In this way, cadmium exhibits a negative effect on both iron and copper homoeostasis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Cadmium / toxicity*
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Copper / metabolism*
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Copper / pharmacology
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Down-Regulation / drug effects
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Down-Regulation / genetics
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Gene Expression Regulation, Fungal / drug effects
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Genes, Fungal / genetics
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Homeostasis / drug effects*
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Iron / metabolism
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Nuclear Proteins / antagonists & inhibitors*
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Nuclear Proteins / chemistry
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Nuclear Proteins / metabolism
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Promoter Regions, Genetic / genetics
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Protein Binding / drug effects
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Protein Transport / drug effects
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Regulon / drug effects
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Regulon / genetics*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / antagonists & inhibitors*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Trans-Activators / antagonists & inhibitors*
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / antagonists & inhibitors*
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Transcription Factors / chemistry
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Transcription Factors / metabolism
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Transcription, Genetic / drug effects
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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MAC1 protein, S cerevisiae
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Nuclear Proteins
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Saccharomyces cerevisiae Proteins
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Trans-Activators
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Transcription Factors
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Cadmium
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Copper
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Iron